〔Abstract〕 Objective To investigate the effects of hypoxia, high glucose single factor and hypoxia high glucose compound factors on the pyroptosis of rat glomerular podocytes. Methods Rat glomerular podocytes were culturedin vitroand randomly divided into control group, high glucose group, hypoxia group and hypoxia high glucose group, EdU method was used to detect the cell proliferation, transmission electron microscope was used to observe the morphology and size changes of nucleus and mitochondria, and Western blot was used to detect pyroptosis related proteins nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), Cysteinyl aspartate specific proteinase-1(Caspase-1), gasdermin(GSDMD) and inflammatory factor pro-interleukin-1β(Pro-IL-1β),interleukin(IL)-1β,IL-18. The effect of hypoxia and high glucose on the pyroptosis of rat glomerular podocytes was analyzed. Results EdU results showed that hypoxia and high glucose inhibited the proliferation ability of rat glomerular podocytes(P<0.05). The results of transmission electron microscopy suggested that hypoxia and high glucose promoted the occurrence of pyroptosis of rat glomerular podocytes. Western blot showed that hypoxia and high glucose promoted pyroptosis of rat glomerular podocytes, and increased the expression of pyroptosis related proteins NLRP3, Caspase-1 and GSDMD, among which the expression of pyroptosis protein increased most significantly in hypoxia and high glucose group(P<0.05). At the same time, it also increased the expression of pro-inflammatory factor Pro-IL-1β, IL-1β and IL-18(P<0.05). Conclusion hypoxia and high glucose can induce pyroptosis of rat glomerular podocytes, one of the mechanisms may be through affecting NLRP3-Caspase-1-GSDMD and its downstream inflammatory factors.